The rapid infusion of citrate anticoagulant during large volume leukapheresis (LVL) results in acute decreases in serum concentrations of the physiologically active (ionized) form of calcium and magnesium leading to citrate toxicity. We studied the effect of prophylactic IV magnesium supplementation on metabolic parameters and citrate-related symptoms. Normal healthy allogeneic donors (n=30) were enrolled in the randomized, placebo-controlled study (placebo=16, IV magnesium=14). All donors received prophylactic IV calcium. Each donor underwent up to three LVL procedures. Magnesium administration lessened the degree of ionized hypomagnesemia and hypocalcemia, and facilitated a longer lasting response of parathyroid gland to decreased serum ionized calcium. In addition, the progressive decreases in serum ionized magnesium concentration seen after repeat LVL procedures in the placebo group were attenuated by magnesium administration. However, magnesium administration did not improve the residual citrate related symptoms. Thus, prophylactic administration of magnesium should be considered only in donors with prior hypomagnesemia or during consecutive LVL procedures. In addition, we investigated the effect of repetitive, frequent (>50 over 10 years) apheresis on bone density of volunteer platelet (n=30) and paid research leukocyte apheresis (n=30) donors , and compared the findings with a control group of whole blood donors (n=30). While there were significant post-apheresis changes in ionized calcium (-25%), intact PTH (=150%), 1,25OH vitamin D (-10%) and all measured bone markers (osteocalcin +39%, C-telopeptides +50%, bone alkaline phosphatase -10%) there were no differences in age / gender / race adjusted bone density scores indicating no detrimental effect of repetitive apheresis on bone density.